Rectal Drug Delivery I

What are the advantages of using rectal drug delivery methods?

Advantages:

• reduce/bypass degradative enzymatic action on drugs (increase drug concentration)

• partially bypass first-pass effect (increase drug concentration)

• ease and convenience of administration

• higher volume/concentration of drug in single dose.

• easy discontinuation (no withdrawal effects → localized effect)

• minimize drug dilution (can be transported dry, in exact dosing and concentration, rectum has lower mucus volume)

How to remember? → suppositories are BIG, rectum is EASILY ACCESSIBLE, rectum has LOWER MUCUS VOLUME, rectum does not have ENZYMES or FIRST-PASS effect, Localized effect → LESS LIKELY/WILL NOT have DRUG WITHDRAWAL SYMPTOMS.

What are the disadvantages of using rectal drug administration

• Not widely accepted

• Difficult administration (alone/caretaker)

• Absorption rate/Effectiveness of drug is dependent on presence of feces.

What are the physiological properties of rectal drug delivery methods?

Quantity of Fluid/Mucus → worry about drug dilution/concentration/absorption rate.

Mucus Properties → pH, consistency (thick/thin)

Circulation Routes → does it go through first-pass effect (superior renal vein) or not (middle and inferior renal vein)

Contents of Rectum → presence of feces

What are the different ways to produce and administer drugs rectally?

Suppositories → solid dosage forms containing suspensions or emulsionshat are meant to melt, soften and dissolve in the rectal cavity to be absorbed in the renal vasculature for localized or systemic effects

Enemas → injectable solutions or suspensions that are meant to be mechanically injected into the rectum and reach the colon for localized treatment.

What is the design for the dosage form of suppositories?

Suppositories are..

1. Tapered on one/both ends → ease of administration → easier/less painful to insert

2. Cylindrical → ease of administration

3. 4 cm long, around 2g in adults and 1g in children → solid suspensions or emulsions

What are the physicochemical properties affecting absorption in the rectum.

• Molecular Size

• Particle Size

• Water/Vehicle Solubility

• Surface Properties

• Drug Concentration

How does surface properties of drug particles affect drug properties or concentration in the body?

Rectal mucus and mucosa→ water-soluble

• if water-soluble (e.g. hydrophilic core, lipophilic exterior) → better dissolution (affects drug concentration)

if oil-soluble (e.g. lipophilic core with lipophilic exterior) → remains in the vehicle, poorer drug dissolution

• determines the type of suppository used

• affects drug release

How does particle size of drug particles affect drug properties or concentration in the body?

The smaller the particle size, the larger the surface area to volume ratio, leading to better drug dissolution and lower sedimentation rate.

• Big: (>150 micrometers) → heavier → higher sedimentation rate

• Small: (>50 micrometers) → lighter → lower sedimentation rate BUT higher agglomeration rate due to VDW forces

Define agglomeration.

Agglomeration is the process of small suspended particles gathering to form small loose clusters or groups within a solution

How does higher drug concentration affect absorption of rectal drugs?

• higher concentration → more particles → agglomeration rate increased → reduced SA:V → reduced absorption

How does larger molecular size affect the absorption of rectally administered drugs?

When there’s larger molecular size → less permeable to membranes → cannot be absorbed readily.

Does patient convenience have the same meaning as patient comfortability?

False. Convenience refers to how easy it is to administer medication. Patient comfortability refers to the patient’s physical and emotional well-being during the administration of the medication.

What do we prescribe in the event that a patient is having a seizure, and drugs cannot be administered orally to ease symptoms?

Rectal Suppositories such as benzodiazepine suppositories that are administered rectally.

What are the different use cases of rectal administration of drugs?

• Not able to administer drugs orally

• Drug is not suitable for oral administration

• Localized treatment is needed to treat certain conditions.